Recently, we and others have developed several cell models for the investigation of the molecular mechanisms underlying the cytotoxicity of nanoparticles of several metallic and non-metallic oxides. These important findings have raised the awareness for the need to derive a set of strategies whereby critical mammalian cell types (e.g., neural cells) can be protected from the cytotoxicity induced by nanoparticles and other nanomaterials. As part of our response to the need to devise a strategy to protect critical cell types against the cytotoxicity induced by nanomaterials, we have continued to develop cell models in vitro to further elucidate and exploit the putative neuroprotective properties of astrocytes-like astrocytoma cells. Previously, we demonstrated the neuroprotection offered by astrocytoma cells to neuroblastma cells in the direct co-culture milieu. The present studies have tested the hypothesis that nanoparticle-induced cytotoxic stress can elicit and/or enhance the neuroprotective effects of astrocytes through the activation of astrocytic signaling and alteration of astroglial function. Furthermore, the neuroprotection can be enhanced in the presence of pioglitazone. Thus, our results may have pathophysiological implications in neuroprotection research but also implication and application in nanotoxicological research